Streptococcus pneumoniae is a well known human pathogen and a major etiologic agent for pneumonia, meningitis, otitis media as well as sepsis, among primarily young children and older adults. Antibodies to a capsular polysaccharide (PS) may provide protection against pneumococci expressing the same capsular serotype. Currently available pneumococcal vaccines contain a mixture of capsular PS of multiple serotypes. For example, one pneumococcal vaccine contains capsular PS from twenty-three commonly found serotypes. The most recently developed type of vaccine contains capsular PS from seven to thirteen serotypes that are conjugated to a protein molecule. A seven-valent conjugate vaccine was introduced in 2000 for clinical use in the USA, and has reduced the incidence of invasive pneumococcal diseases in children and in adults.
An alternative approach for protecting children and the elderly from pneumococcal infection employs protein antigens that could elicit protective immune responses. Such proteins may serve as a vaccine by themselves, may be used in conjunction with successful polysaccharide-protein conjugates, or serve as carriers for polysaccharide components. The pneumococcal surface protein A (PspA) has been identified as an immunogenic protein with potential for pneumococcal vaccines.
Most of the work concerning PspA as a potential for a protein-based pneumococcal vaccine has focused on cross-protective epitopes lying within the alpha-helical region of the PspA protein, a region predicted to have a coiled-coil protein conformation. It has been suggested, however, that this alpha-helical region may have the potential to elicit antibodies that cross-react with proteins of the human heart and skeletal muscles. On the other hand, adults often have PspA antibodies, naturally elicited during childhood, that have no connection to rheumatic heart disease or auto-reactive immune syndromes. Nevertheless, there remains a need for pneumococcal surface polypeptides that are immunogenic yet minimize risk of self-reactive responses.